Regional Patterns of Fluid and Fat Accumulation in Patients with Lower Extremity Lymphedema Using Magnetic Resonance Angiography.

BACKGROUND: Fat accumulation is frequently observed in patients with lymphedema but is not accounted for in existing staging systems. In addition, the specific regional patterns of fat and fluid accumulation remain unknown and might affect outcomes following medical or surgical intervention. The purpose of this study was to evaluate fluid and fat distribution in patients with lower extremity lymphedema using magnetic resonance angiography. METHODS: Magnetic resonance angiographic examinations of patients with lower extremity lymphedema were reviewed. Fluid-fat grade and location were assessed by three observers. Three-point scales were developed to grade fluid (0 = no fluid, 1 = reticular pattern of fluid, and 2 = continuous stripe of subcutaneous fluid) and fat (0 = normal, 1 = subcutaneous thickness less than twice that of the unaffected side, and 2 = subcutaneous thickness greater than twice that of the unaffected side) accumulation. RESULTS: In total, 76 magnetic resonance angiographic examinations were evaluated. Using the proposed grading system, there was good interobserver agreement for fat and fluid accumulation location (91.5 percent; κ = 0.9), fluid accumulation grade (95.7 percent; κ = 0.95), and fat accumulation grade (87.2 percent; κ = 0.86). Patients with International Society of Lymphology stage 2 lymphedema had a wide range of fluid and fat grades (normal to severe). The most common location of fluid accumulation was the lateral lower leg, whereas the most common location of fat accumulation was the medial and lateral lower leg. CONCLUSION: The proposed magnetic resonance angiographic grading system may help stratify patients with International Society of Lymphology stage 2 lymphedema on the basis of tissue composition. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

Three-dimensional modelling of the femur and humerus in adult male guinea pigs (guinea pig) with computed tomography and some biometric measurement values.

BACKGROUND: Guinea pig is a species belonging to the Caviidae family of the Rodentia order and is frequently used in experimental studies. Biomedical imaging methods are used in the diagnosis and treatment of many diseases in medicine. Among these methods, computed tomography (CT) is one of the most important imaging methods. In this study, it was aimed to perform the three-dimensional (3D) modelling of the CT images, obtained from the humerus and femur in the guinea pigs, via the MIMICS programme, and to make some biometric measurements regarding the bones over these models. MATERIALS AND METHODS: In the present study, 12 male adult guinea pigs were used. The soft tissue on the humerus and femur bones of the guinea pigs was removed. After this procedure, CT images at a 0.5 mm-thickness were obtained from the animals. The images were recorded in DICOM format. Then, the reconstruction process was performed from the images by using the 3D modeling programme MIMICS® 13.1. On the 3D model of the humerus and femur (right-left), volumes, surface areas and lengths as well as other biometric parameters were measured separately, and the values were recorded. In addition, measurements of the bones were made with the help of a digital calliper. RESULTS: Among the parameters obtained from 3D models, a statistical difference was observed between the right and left cortical thicknesses of the femur from the measurements of calliper and the right and left humerus volumes (p < 0.05); whereas, no statistical difference was found in other parameters of both measurements (p > 0.05). CONCLUSIONS: It can be stated that CT and 3D modelling can be used for the measurement of some parameters in the long bones of the guinea pigs.

Morphometric and macroanatomic examination of auditory ossicles in male wolves (Canis lupus).

BACKGROUND: The aim of the study was to determine morphometric and macroanatomic features of auditory ossicles and the tympanic bulla in wolf. MATERIALS AND METHODS: For this purpose, 7 skulls of adult male wolf were used in the study. Auditory ossicles was photographed on a dissection microscope after it was removed from the skull. A total of 14 morphometric measurements were taken among the different points of malleus, incus and stapes in Image J programme. Mean values of the measurements were obtained and statistically compared in terms of sides (right-left). RESULTS: In male wolves, the lengths of the right and left malleus were determined as mean 9.35 ± 0.14 and 9.57 ± 0.25 mm, the lengths of the incus as mean 3.01 ± 0.32 and 2.94 ± 0.16 mm, and the lengths of the stapes as mean 2.57 ± 0.12 and 2.59 ± 0.14 mm, respectively. The differences were not statistically significant when all the morphometric parameters were compared in terms of sides (p > 0.05). CONCLUSIONS: It is considered that this study will contribute to the anatomical studies to be conducted in the Canidae family regarding auditory ossicles.

Blind mole rat (Spalax leucodon) masseter muscle: structure, homology, diversification and nomenclature.

BACKGROUND: It is well known that rodents are defined by a unique masticatory apparatus. The present study describes the design and structure of the masseter muscle of the blind mole rat (Spalax leucodon). The blind mole rat, which emer- ged 5.3-3.4 million years ago during the Late Pliocene period, is a subterranean, hypoxia-tolerant and cancer-resistant rodent. Yet, despite these impressive cha- racteristics, no information exists on their masticatory musculature. MATERIALS AND METHODS: Fifteen adult blind mole rats were used in this study. Dissections were performed to investigate the anatomical characteristics of the masseter muscle. RESULTS: The muscle was comprised of three different parts: the superficial mas- seter, the deep masseter and the zygomaticomandibularis muscle. The superficial masseter originated from the facial fossa at the ventral side of the infraorbital foramen. The deep masseter was separated into anterior and posterior parts. The anterior part of the zygomaticomandibularis muscle arose from the snout and passed through the infraorbital foramen to connect on the mandible. CONCLUSIONS: The construction of the deep masseter and zygomaticomandibularis muscles were of the Myomorpha type. Further studies are needed to reveal features such as muscle biomechanics, muscle types.

Dark Rims: Novel Sequence Enhances Diagnostic Specificity in Multiple Sclerosis.

BACKGROUND AND PURPOSE: The 2010 McDonald criteria are designed to sensitively detect MS; however, the low specificity of these criteria can occasionally lead to the misdiagnosis of MS. The purpose of this study was to determine whether a novel double inversion recovery MR imaging technique has the potential to increase the specificity of diagnostic criteria distinguishing MS from non-MS white matter lesions. MATERIALS AND METHODS: This was a cross-sectional observational study. MR imaging data were acquired between 2011 and 2016. A novel double inversion recovery sequence that suppresses CSF and GM signal was used (GM-double inversion recovery). We compared WM lesions in a group of patients with multiple sclerosis and in a second group of positive controls with white matter lesions who did not have a diagnosis of MS. The presence of a rim on the GM-double inversion recovery MR imaging sequence was combined with the 2001 and 2010 McDonald disseminated-in-space criteria. Multiple MR imaging markers, including lesion location, size, and the presence of a rim, were compared between groups as well as a quantitative measure of lesion T1 hypointensity. RESULTS: MR images from 107 patients with relapsing-remitting MS (median age, 32 years) and 36 positive control (median age, 39 years) subjects were analyzed. No significant differences were found in age and sex. In patients with MS, 1120/3211 lesions (35%) had a rim on GM-double inversion recovery; the positive control group had only 9/893 rim lesions (1%). Rims were associated with a decrease in the lesion T1 ratio. Using the 2010 MR imaging criteria plus the presence of rims on GM-double inversion recovery, we achieved 78% and 97% specificity in subjects with ≥1 and ≥2 rim lesions, respectively. CONCLUSIONS: The addition of a novel GM-double inversion recovery technique enhanced specificity for diagnosing MS compared with established MR imaging criteria.

Effects of bisphenol A on antioxidant system and lipid profile in rats.

We investigated the effects of bisphenol A (BPA) on antioxidant system enzymes, blood lipid profile and histologic structure of liver and pancreas in rats. We used 40 8-week-old male Wistar albino rats. The animals were divided into five groups of eight: control, vehicle, BPA-5, BPA-50 and BPA-500. BPA was dissolved in ethanol, then mixed with corn oil. The control group was untreated. The vehicle group was given the ethanol-corn oil mixture. The BPA 5, BPA 50 and BPA 500 groups were given 5, 50, and 500 µg/kg body weights/day, respectively. After 8 weeks, blood and tissue samples were obtained from the animals and plasma GSH, TBARS, SOD, GPx, CAT, NO, total cholesterol, triglyceride, HDL, LDL, insulin and glucose were measured. The sections were stained using histochemical and immunohistochemical methods. BPA significantly decreased the levels of GSH, SOD, GPx and CAT, and increased the levels of TBARS and NO in plasma. There was no significant difference among the groups in plasma insulin and glucose levels. The percentage of insulin immunoreactive cells in islets increased significantly in the BPA-500 group. The H-score of the BPA-5 and BPA-50 groups decreased significantly compared to controls. We found that BPA caused oxidative stress and disruption of pancreatic ß-cell function. Therefore, BPA is a risk factor for animal and human health.

Modeling the relationship among gray matter atrophy, abnormalities in connecting white matter, and cognitive performance in early multiple sclerosis.

BACKGROUND AND PURPOSE: Quantitative assessment of clinical and pathologic consequences of white matter abnormalities in multiple sclerosis is critical in understanding the pathways of disease. This study aimed to test whether gray matter atrophy was related to abnormalities in connecting white matter and to identify patterns of imaging biomarker abnormalities that were related to patient processing speed. MATERIALS AND METHODS: Image data and Symbol Digit Modalities Test scores were collected from a cohort of patients with early multiple sclerosis. The Network Modification Tool was used to estimate connectivity irregularities by projecting white matter abnormalities onto connecting gray matter regions. Partial least-squares regression quantified the relationship between imaging biomarkers and processing speed as measured by the Symbol Digit Modalities Test. RESULTS: Atrophy in deep gray matter structures of the thalami and putamen had moderate and significant correlations with abnormalities in connecting white matter (r = 0.39-0.41, P < .05 corrected). The 2 models of processing speed, 1 for each of the WM imaging biomarkers, had goodness-of-fit (R(2)) values of 0.42 and 0.30. A measure of the impact of white matter lesions on the connectivity of occipital and parietal areas had significant nonzero regression coefficients. CONCLUSIONS: We concluded that deep gray matter regions may be susceptible to inflammation and/or demyelination in white matter, possibly having a higher sensitivity to remote degeneration, and that lesions affecting visual processing pathways were related to processing speed. The Network Modification Tool may be used to quantify the impact of early white matter abnormalities on both connecting gray matter structures and processing speed.

Three-dimensional reconstruction of New Zealand rabbit antebrachium by multidetector computed tomography.

The aim of this study was to reveal biometric peculiarities of New Zealand white rabbit antebrachium (radius and ulna) by means of three-dimensional (3D) reconstruction of multidetector computed tomography (MDCT) images. Under general anesthesia, the antebrachiums of a total of sixteen rabbits of both sexes were scanned with a general diagnostic MDCT. Biometric measurements of the reconstructed models from high resolution MDCT images were analyzed statistically. Consequently, when biometric measurement values of corresponding bones of antebrachium were compared, it was revealed that there was no statistical significance within both sexes but there were statistically important differences between both sexes in some biometric measurements. It has been suggested that the results from the study can shed light on future studies on the skeletal system and can form a modern point of view to anatomical education.

Delayed leptin administration after stroke induces neurogenesis and angiogenesis.

Leptin is a potent AMP kinase (AMPK) inhibitor that induces neuroprotection, neurogenesis, and angiogenesis when administered immediately after stroke. To dissociate these effects, we explored the effects of delayed administration of leptin, at 10 days after stroke onset, on neurogenesis and angiogenesis after stroke. Sabra mice underwent photothrombotic stroke and were treated with vehicle or leptin given either as a single dose or in triple dosing, 10 days later. Newborn cells were labeled with bromodeoxyuridine. Functional outcome was studied with the neurological severity score for 90 days poststroke, and the brains were then evaluated via immunohistochemistry. Final infarct volumes did not differ between the groups. Exogenous leptin led to significant increments in the number of proliferating BrdU(+) cells in the subventricular zone and in the cortex abutting the lesion (2.5-fold and 1.4-fold, respectively). There were significant increments in the number of newborn neurons and glia (4- and 3.4-fold, respectively) in leptin-treated animals. Leptin also significantly increased the number of blood vessels in the perilesioned cortex. However, animals treated with leptin failed to demonstrate significantly better functional states. In conclusion, leptin induces neurogenesis and angiogenesis even when given late after stroke but does not lead to better functional outcome in this delayed-treatment paradigm. These results suggest that the main beneficial effects of leptin after stroke are associated with its early neuroprotective role rather than with its proneurogenic or proangiogenic effects.

Leptin induces neuroprotection neurogenesis and angiogenesis after stroke.

Leptin is a potent AMP kinase (AMPK) inhibitor that is central to cell survival. Hence, we explored the effects of leptin on neurogenesis and angiogenesis after stroke. Neural stem cells (NSC) were grown as neurospheres in culture and treated with vehicle or leptin and neurosphere size and terminal differentiation were then determined. We then explored the effects of leptin on endogenous repair mechanisms in vivo. Sabra mice underwent photothrombotic stroke, were given vehicle or leptin and newborn cells were labeled with Bromo-deoxy-Uridine. Functional outcome was studied with the neurological severity score for 90 days post stroke and the brains were then evaluated with immunohistochemistry. In a subset of animals the brains were also evaluated for changes in the expression of leptin receptor and AMPK. In vitro, leptin led to a 2-fold increase in neurosphere size but did not change the differentiation of newborn cells. Following stroke, exogenous leptin led to a 4-fold increase in the number of NSC in the cortex abutting the lesion. There was a 1.5-fold increase in the number of newborn neurons and glia in leptin treated animals. Leptin also significantly increased the number of blood vessels in the peri-lesioned cortex. Leptin treated mice had increased expression of leptin receptor and increased phosphorylated AMPK concentration. Animals treated with leptin also had significantly better functional states. In conclusion, leptin induces neurogenesis and angiogenesis after stroke and leads to increased leptin receptor and pAMPK concentrations. This may explain at least in part the better functional outcome observed in leptin treated animals after stroke.

Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of autoantibodies directed against an epitope of the glutamate/N-methyl-D-aspartic acid (NMDA) receptor subunit NR2A (which is highly expressed in human brain) in the sera of lupus patients, and to investigate the possible correlation of these antibodies with clinical and serological manifestations of systemic lupus erythematosus (SLE). METHODS: Sera were obtained from 109 consecutive SLE patients. Controls were 65 patients with myasthenia gravis, 19 with autoimmune polyendocrine syndrome type I (APS I), and 65 healthy donors. A 15 amino acid long peptide based on a sequence within the NR2A subunit of the NMDA/glutamate receptor was synthesised. Antibodies to this peptide were determined by enzyme linked immunosorbent assay. Antibodies against double stranded DNA (dsDNA) were measured by Chrithidia luciliae assay. Disease activity was determined using the SLE disease activity index (SLEDAI). RESULTS: Sera of 34/109 SLE patients (31%) reacted specifically with the NR2A peptide compared with only 4/65 myasthenia gravis patients (6.1%, p<0.001), 1/19 APS I patients (5.3%, p<0.02), and 3/65 healthy controls (4.6%, p<0.001). No correlation was found between the presence of NR2A and dsDNA or anti-cardiolipin specific autoantibodies. In addition, no significant correlation was observed between the presence of NR2A specific antibodies and the SLEDAI score or any lupus related clinical manifestations. CONCLUSIONS: A significant number of SLE patients (31%) have NR2A specific antibodies that do not correlate with anti-dsDNA antibodies. Additional studies of lupus patients with neurological disorders should elucidate the role of NR2A specific antibodies in lupus related CNS manifestations.

Use of colour duplex ultrasound to diagnose giant cell arteritis in a case of visual loss of uncertain aetiology.

Giant cell arteritis is a common condition that can result in permanent visual loss. It has traditionally been diagnosed by invasive temporal artery biopsy in cases of clinical suspicion. The findings of colour duplex ultrasound have recently been described. We report the use of duplex ultrasound to diagnose temporal arteritis, with clinicopathological correlation, and discuss the possible application of this non-invasive technique to the management of giant cell arteritis.

Modulation of autoreactive responses of peripheral blood lymphocytes of patients with systemic lupus erythematosus by peptides based on human and murine anti-DNA autoantibodies.

Two peptides, based on the sequences of the complementarity-determining regions (CDR) 1 and 3 of a pathogenic murine monoclonal anti-DNA autoatibody that bears the 16/6 idiotype (Id), were shown to either prevent or treat an already established systemic lupus erythematosus (SLE) in two murine models of lupus. Two additional peptides based on the human monoclonal anti-DNA, 16/6 Id were synthesized. This study was undertaken in order to investigate the ability of the CDR-based peptides to immunomodulate SLE-associated responses of peripheral blood lymphocytes (PBL) of SLE patients. PBL of 24 of the 62 SLE patients tested proliferated in vitro following stimulation with the human 16/6 Id. Peptides based on the CDRs of both the human and murine anti-DNA autoantibodies inhibited efficiently and specifically the 16/6 Id-induced proliferation and IL-2 production. The latter inhibitions correlated with an up-regulated production (by 2.5-3.5-fold) of the immunosuppressive cytokine, TGF-beta. Overall, the results of our study demonstrate that the CDR-based peptides are capable of down-regulating in vitro autoreactive T cell responses of PBL of SLE patients. Thus, these peptides are potential candidates for a novel specific treatment of SLE patients.

Effect of prior steroid treatment on temporal artery biopsy findings in giant cell arteritis.

AIM: To examine the effect of up to 6 weeks of corticosteroid treatment on the positive temporal artery biopsy rate in giant cell arteritis (GCA). METHODS: Prospective comparative clinical study of 11 patients meeting the American College of Rheumatology criteria for diagnosis of GCA. Patients underwent temporal artery biopsy within 1 week, at 2-3 weeks, or after 4 weeks of corticosteroid treatment. RESULTS: Overall, nine of 11 (82%) patients had positive temporal artery biopsies. Six of seven (86%) biopsies performed after 4 or more weeks of steroid treatment were positive. CONCLUSION: Temporal artery biopsy is useful several weeks after institution of steroids.

Activity of matrix metalloproteinase-9 is elevated in sera of patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the increased production of autoantibodies and by systemic clinical manifestations and damage to multiple organs. The aim of the present study was to analyse matrix metalloproteinase (MMP)-9 activity in sera of patients with active and inactive SLE in order to evaluate its role in the pathogenesis and course of the disease, as well as its diagnostic value. We measured activity levels of MMP-9 and MMP-2, using both gel zymography and activity assay kits, in sera of 40 SLE patients and of 25 healthy controls. We found that MMP-9 activity, but not MMP-2 activity, is significantly elevated in the sera of SLE patients compared with sera samples of healthy controls. High activity levels of MMP-9 were determined in sera of 68% of the SLE patients. Elevated levels of MMP-9 were correlated with the presence of discoid rash, Raynaud phenomenon, pneumonitis, mucosal ulcers and anti-phospholipid antibodies. Changes in activity levels of MMP-9, but not of MMP-2, were observed in sera of the same patient at different periods of the disease course. High levels of MMP-9 did not correlate with disease activity index (SLEDAI, BILAG) in female patients, but correlated with SLE activity in the group of male patients. The results of the present study suggest that MMP-9 plays a role in the pathogenesis of SLE.

Ginseng improves pulmonary functions and exercise capacity in patients with COPD.

Ginseng is a root that has been used to treat patients with various illnesses for the last 2000 years. The purpose of this study was to evaluate the effects of Ginseng extract (G115) on Pulmonary Function Tests (PFTs), Maximum Voluntary Ventilation (MVV), Maximum Inspiratory Pressure (MIP) and Maximal Oxygen Consumption (VO2max) in patients with moderately-severe Chronic Obstructive Pulmonary Disease (COPD). Ninety-two adults were randomly divided into the experimental (n = 49, G115 100 mg bid for three months) and placebo-control (n = 43) groups. PFTs, MVV and MIP were studied before treatment and every two weeks for the 3-month-study period. Exercise test and VO2max measurements were performed before the beginning and after six weeks and three months. P lower than 0.05 was considered significant. Baseline demographics and pulmonary parameters were similar between the groups. In the experimental, but not in the control group, all parameters significantly increased above baseline and compared with the placebo group. Maximum increase, compared with baseline was FVC-32.5%, FEV1.0-27.0%, PEF-27.5%, FEF50-45.4%, FEF75-56.9%, MVV-40.4%, MIP-47.0% and VO2max-37.5%. No side effects were observed. G115 100 mg bid for three months, but not placebo, improved PFTs, MVV, MIP and VO2 max in patients with moderately-severe COPD with no side effects.

Quantification of relative afferent pupillary defects induced by posterior sub-Tenon's, peribulbar, and retrobulbar anaesthetics.

AIMS: The effect of local anaesthetics on optic nerve function can be investigated by quantifying the relative afferent pupillary defect (RAPD). METHODS: The study compared the depth of induced RAPD following posterior sub-Tenon's, retrobulbar, and peribulbar local anaesthetics using crossed polarising filters before cataract surgery (time 1 = 5 minutes), immediately after surgery (time 2 = 42 minutes (av)), and once again on the ward (time 3 = 107 minutes (av)). RESULTS: All patients developed a RAPD. There was no significant difference in the depth of RAPD between the groups at any one time period. The peribulbar group had a significantly steeper decay in RAPD from time 1 to time 2 (p = 0.014). This effect was reduced when the shorter operation time for this group was entered as a cofactor (p = 0.063). By time 3 the RAPDs for all groups had decayed similarly so that no differences could be detected. CONCLUSION: All three anaesthetic methods caused a similar level of disruption to optic nerve conduction immediately following administration and at the time of day case discharge.

Suppression of experimental systemic lupus erythematosus (SLE) in mice via TNF inhibition by an anti-TNFalpha monoclonal antibody and by pentoxiphylline.

We have previously shown that the clinical manifestations of experimental systemic lupus erythematosus (SLE) correlate with an early increased secretion of TNFalpha and IL-1. In the present study, we examined the efficacy of two therapeutic modalities which lower TNFalpha production or activity, on the clinical manifestations of the disease. Experimental SLE was induced in naive C3H.SW mice by injection of the human anti-DNA monoclonal antibody (mAb) bearing the common idiotype, 16/6 Id. Two weeks after booster injections, treatment with either an anti-TNFalpha mAb, or pentoxiphylline (PTX) was started, for a period of 6 weeks. Production of TNFalpha (by splenocytes) and IL-1 (by peritoneal macrophages) was determined 3 and 7 months after disease induction. The experimental mice were also followed for disease manifestations. Both treatment protocols, with anti-TNFalpha mAb and with PTX, reduced the production of the two pro-inflammatory cytokines. TNFalpha and IL-1, in mice with experimental SLE. Anti-DNA antibodies were significantly lower in the mice treated with either protocol. In addition, a significantly lower rate of leukopenia, proteinuria and immune complex deposition was observed in treated mice. Abrogation of TNFalpha and IL-1 production in the early stages of experimental SLE by an anti-TNFalpha mAb or by PTX improves the clinical status of mice afflicted with this autoimmune disease.

Clinical comparison of the measurement of the IOP with the ocular blood flow tonometer, the Tonopen XL and the Goldmann applanation tonometer.

PURPOSE: In addition to measuring ocular blood flow, the ocular blood flow tonometer (OBF) can also be set to solely record intraocular pressure (IOP). In this mode it provides a quick means of tonometry which may allow nursing staff to be more easily trained in its use than conventional Goldmann tonometry. With a view to its eventual use in nurse-led clinics we undertook a study to compare both the OBF tonometer and our currently favoured nurse practitioners tonometer the tonopen XL with Goldmann tonometry. METHOD: IOP was measured in 99 eyes with all three tonometers in a random order. RESULTS: There was not any statistically significant difference between the measurements of all three tonometers. CONCLUSIONS: It is concluded that OBF tonometer can provide clinically useful measurements of intraocular pressure which may in fact be more accurate than the tonopen, however, our opinion is that it possibly is not suitable for a universal glaucoma clinics application.